The comorbidity of alcohol and tobacco use has been a central theme of ongoing MARC investigations. Existing MARC-affiliated studies have used epidemiological, behavior genetic, and laboratory methods to understand the robust associations between drinking and smoking. To date, however, the MARC research portfolio has not included studies that bridge the basic laboratory research with the genetic epidemiology. Consequently, relatively little is known about the motivational mechanisms that contribute to the joint use of alcohol and tobacco in actual users living in their natural environments. Using Ecological Momentary Assessment to investigate hypothesized mechanisms that purportedly motivate joint use of alcohol and cigarettes, we will prospectively assess alcohol use and smoking, their subjective antecedents and sequelae, and environmental contexts in 400 smokers and 200 nonsmokers recruited from the community. Electronic diary recording, which will include morning assessments, drinking episode assessments, and smoking episode assessments, as well as random prompts, will occur over a 3-week period. This design will permit within-subjects contrasts in the drinker-smokers that characterize the unique motivational sequelae of joint drinking-smoking moments relative to moments when only drinking, only smoking, or neither are taking place. Additional comparisons between drinker-smokers and drinkers only will be used to identify domains where chronic effects of smoking (e.g., chronic cross-tolerance) or other stable individual differences that differentiate smoking and nonsmoking drinkers may contribute to the pattern of motivational effects seen in drinker-smokers. Using hierarchical linear modeling, and to a lesser extent, survival analysis, unique effects of conjoint alcohol-smoking, relative to smoking alone and drinking alone, on both positive and negative affective states will be explored, and the relation between individual differences in conjoint alcohol-smoking and substance-specific changes in positive/negative affect and subsequent drinking and smoking behavior will be examined. Also, the extent to which individual difference variables (e.g., sensation-seeking; escapist motives for substance use) condition the magnitude of conjoint and substance-specific effects on alcohol and/or tobacco seeking behavior will be determined. In addition, the current study will determine the association between smoking level and acute and delayed aversive (punishing) effects of alcohol, and will characterize the extent to which individual differences in these aversive consequences predict subsequent drinking behavior.